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Updated: Mar 29, 2026
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Prediction of Protein-Ligand Binding Structures by Replica-Exchange Umbrella Sampling Simulations: Application to
Hironori Kokubo1, Toshimasa Tanaka1, Yuko Okamoto2,3,4,5
1Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical , 26-1 Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8585, Japan.
Abstract:
We have applied our prediction method, which is based on the replica-exchange umbrella sampling for protein-ligand binding structures, to two kinase systems (p38 and JNK3) with two different ligand molecules for each kinase. Starting from configurations in which the protein and the ligand are far away from each other, our method predicted the ligand binding structures in excellent agreement with the experimental data from PDB in all four cases, which suggests the general applicability of our method to kinase systems. In addition, the protein flexibility was shown to be essential to predict the correct binding structure for one of the systems, where dihydroquinolinone was bound to p38 alpha kinase (PDB ID: 1OVE ).
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